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Inhibition of Inducible Nitric Oxide Synthase Expression by a Novel Small Molecule Activator of the Unfolded Protein Response
The transcription of inducible nitric oxide synthase (iNOS) is activated by a network of proinflammatory signaling pathways. Here we describe the identification of a small molecule that downregulates the expression of iNOS mRNA and protein in cytokine-activated cells and suppresses nitric oxide prod...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Bentham Open
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803434/ https://www.ncbi.nlm.nih.gov/pubmed/20161838 http://dx.doi.org/10.2174/1875397300802010001 |
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author | Symons, Kent T Massari, Mark E Dozier, Sara J Nguyen, Phan M Jenkins, David Herbert, Mark Gahman, Timothy C Noble, Stewart A Rozenkrants, Natasha Zhang, Yan Rao, Tadimeti S Shiau, Andrew K Hassig, Christian A |
author_facet | Symons, Kent T Massari, Mark E Dozier, Sara J Nguyen, Phan M Jenkins, David Herbert, Mark Gahman, Timothy C Noble, Stewart A Rozenkrants, Natasha Zhang, Yan Rao, Tadimeti S Shiau, Andrew K Hassig, Christian A |
author_sort | Symons, Kent T |
collection | PubMed |
description | The transcription of inducible nitric oxide synthase (iNOS) is activated by a network of proinflammatory signaling pathways. Here we describe the identification of a small molecule that downregulates the expression of iNOS mRNA and protein in cytokine-activated cells and suppresses nitric oxide production in vivo. Mechanistic analysis suggests that this small molecule, erstressin, also activates the unfolded protein response (UPR), a signaling pathway triggered by endoplasmic reticulum stress. Erstressin induces rapid phosphorylation of eIF2α and the alternative splicing of XBP-1, hallmark initiating events of the UPR. Further, erstressin activates the transcription of multiple genes involved in the UPR. These data suggest an inverse relationship between UPR activation and iNOS mRNA and protein expression under proinflammatory conditions. |
format | Text |
id | pubmed-2803434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | Bentham Open |
record_format | MEDLINE/PubMed |
spelling | pubmed-28034342010-02-16 Inhibition of Inducible Nitric Oxide Synthase Expression by a Novel Small Molecule Activator of the Unfolded Protein Response Symons, Kent T Massari, Mark E Dozier, Sara J Nguyen, Phan M Jenkins, David Herbert, Mark Gahman, Timothy C Noble, Stewart A Rozenkrants, Natasha Zhang, Yan Rao, Tadimeti S Shiau, Andrew K Hassig, Christian A Curr Chem Genomics Article The transcription of inducible nitric oxide synthase (iNOS) is activated by a network of proinflammatory signaling pathways. Here we describe the identification of a small molecule that downregulates the expression of iNOS mRNA and protein in cytokine-activated cells and suppresses nitric oxide production in vivo. Mechanistic analysis suggests that this small molecule, erstressin, also activates the unfolded protein response (UPR), a signaling pathway triggered by endoplasmic reticulum stress. Erstressin induces rapid phosphorylation of eIF2α and the alternative splicing of XBP-1, hallmark initiating events of the UPR. Further, erstressin activates the transcription of multiple genes involved in the UPR. These data suggest an inverse relationship between UPR activation and iNOS mRNA and protein expression under proinflammatory conditions. Bentham Open 2008-09-27 /pmc/articles/PMC2803434/ /pubmed/20161838 http://dx.doi.org/10.2174/1875397300802010001 Text en © Symons et al.; Licensee Bentham Open. http://creativecommons.org/licenses/by-nc/3.0/ This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Article Symons, Kent T Massari, Mark E Dozier, Sara J Nguyen, Phan M Jenkins, David Herbert, Mark Gahman, Timothy C Noble, Stewart A Rozenkrants, Natasha Zhang, Yan Rao, Tadimeti S Shiau, Andrew K Hassig, Christian A Inhibition of Inducible Nitric Oxide Synthase Expression by a Novel Small Molecule Activator of the Unfolded Protein Response |
title | Inhibition of Inducible Nitric Oxide Synthase Expression by a Novel Small Molecule Activator of the Unfolded Protein Response |
title_full | Inhibition of Inducible Nitric Oxide Synthase Expression by a Novel Small Molecule Activator of the Unfolded Protein Response |
title_fullStr | Inhibition of Inducible Nitric Oxide Synthase Expression by a Novel Small Molecule Activator of the Unfolded Protein Response |
title_full_unstemmed | Inhibition of Inducible Nitric Oxide Synthase Expression by a Novel Small Molecule Activator of the Unfolded Protein Response |
title_short | Inhibition of Inducible Nitric Oxide Synthase Expression by a Novel Small Molecule Activator of the Unfolded Protein Response |
title_sort | inhibition of inducible nitric oxide synthase expression by a novel small molecule activator of the unfolded protein response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803434/ https://www.ncbi.nlm.nih.gov/pubmed/20161838 http://dx.doi.org/10.2174/1875397300802010001 |
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